The susceptibility of the developing nervous system to environmental agents has been a major concern with regard to children's health issues. While current exposure levels to environmental agents does not represent an acute injury, disruption to the nervous system may be associated with either a structural alteration in the formation of the neural network and/or in nervous system functioning. It is the goal of this project to develop and validate test methods that will allow us to assess various types of chemical-induced perturbations of the brain during development. The formation and interactions between the various cell types in the brain are critically timed events.Such windows of vulnerability is assummed to be a major component in the differential susceptibility of the developing organism to environmental insult. This project examines chemical induced perturbations during development of the nevous as indicated by various alterations in the morphology and molecular profile in the developing brain and assoicated neurobehavioral outcome of such exposure. The specific projects under study include 1) distribution of mercury to the brain of young animals following the intramuscular injection of various mercuricals including methylmercury, ethylmercury and the vaccine perservative, thimerosal. 2) Alterations in neuronal processes in the brain following exposure to compounds that perturb homeostatic maintenance of thyroid hormone during gestational and postnatal development. Early developmental exposure to inorganic lead is known to alter brain development. Based upon our previous studies examining specific neuronal and glia markers following low level lead exposure we initiated a study to examine in a more broad manner the developmental ontogeny of multiple nervous system specific genes using cDNA microarray techniques. One specific finding of these studies was the shift in the developmental pattern for a specific chlorid plexus gene suggesting an early maturation of the chlorid plexus as a protective mechanism against a heavy metal exposure however, the consequences to such an early maturation is yet to be studied. For these studies we continue to use a number of methods to examine alterations in the developing nervous system following exposure to environmental agents including immunohistochemistry, molecular techniques to examine mRNA levels, as well as assessment of neurobehavioral functioning.